tbuckley/cabot-search huggingface dataset:
Symmetrical sporotrichosis on the face: pathogen spread from the nose along both sides of facial lymphatic vessels?
Authors: Zimeng You, Yuping Ran
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Symmetrical sporotrichosis on the face: pathogen spread from the nose along both sides of facial lymphatic vessels? Get access Zimeng You, Zimeng You Conceptualization, Formal analysis, Methodology, Writing - original draft Department of DermatovenereologyLaboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-related Molecular NetworkAcademician Workstation of Wanqing Liao, West China Hospital, Sichuan University, Chengdu, China https://orcid.org/0000-0001-7333-2223 Search for other works by this author on: Oxford Academic Google Scholar Yuping Ran Yuping Ran Formal analysis, Funding acquisition, Methodology, Writing - review & editing Department of DermatovenereologyLaboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-related Molecular NetworkAcademician Workstation of Wanqing Liao, West China Hospital, Sichuan University, Chengdu, China Correspondence: Yuping Ran. Email: ranyuping@vip.sina.com https://orcid.org/0000-0002-9382-0571 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad307, https://doi.org/10.1093/bjd/ljad307 Published: 23 August 2023 Article history Received: 10 July 2023 Revision received: 17 August 2023 Accepted: 20 August 2023 Published: 23 August 2023 Corrected and typeset: 14 September 2023
<i>MGMT</i> Promoter Methylation Predicts Overall Survival after Chemotherapy for 1p/19q-Codeleted Gliomas
Authors: Connor J. Kinslow, Ali I. Rae, Kekoa Taparra, Prashanth Kumar, Markus D. Siegelin, Jack Grinband, Brian J.A. Gill, Guy M. McKhann, Michael B. Sisti, Jeffrey N. Bruce, Peter D. Canoll, Fabio M. Iwamoto, David P. Horowitz, Lisa A. Kachnic, Alfred I. Neugut, James B. Yu, Simon K. Cheng, Tony J.C. Wang
Journal: Clinical Cancer Research (2023)

Abstract Purpose: While MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent data suggest that mMGMT is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated. Experimental Design: We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known MGMT promoter status in the National Cancer Database from 2010 to 2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of mMGMT on OS after adjusting for age, sex, race, comorbidity, grade, extent of resection, chemotherapy, and radiotherapy. Results: We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 1,009 (77.8%) patients. Unmethylated MGMT (uMGMT) was associated with worse survival compared with mMGMT [70% {95% confidence interval (CI), 64%–77%} vs. 81% (95% CI, 78%–85%); P &amp;lt; 0.001; adjusted HR (aHR), 2.35 (95% CI, 1.77–3.14)]. uMGMT was associated with worse survival in patients who received chemotherapy [63% (95% CI, 55–73%) vs. 80% (95% CI, 76%–84%); P &amp;lt; 0.001; aHR, 2.61 (95% CI, 1.89–3.60)] but not in patients who did not receive chemotherapy [P = 0.38; HR, 1.31 (95% CI, 0.71–2.42)]. Similar results were observed regardless of World Health Organization grade and after single- or multiagent chemotherapy. Conclusions: Our study demonstrates an association between mMGMT and OS in 1p/19q-codeleted gliomas. MGMT promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint.
CDK4/6 Inhibition Sensitizes Intracranial Tumors to PD-1 Blockade in Preclinical Models of Brain Metastasis
Authors: Naema Nayyar, Magali A. de Sauvage, Jane Chuprin, Emily M. Sullivan, Mohini Singh, Consuelo Torrini, Britney S. Zhang, Sushobhana Bandyopadhyay, Keith A. Daniels, Christopher Alvarez-Breckenridge, Ashish Dahal, Michael A. Brehm, Priscilla K. Brastianos
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Brain metastases are associated with high morbidity and are often resistant to immune checkpoint inhibitors. We evaluated whether CDK4/6 inhibitor (CDKi) abemaciclib can sensitize intracranial tumors to programmed cell death protein 1 (PD-1) inhibition in mouse models of melanoma and breast cancer brain metastasis. Experimental Design: Treatment response was evaluated in vivo using immunocompetent mouse models of brain metastasis bearing concurrent intracranial and extracranial tumors. Treatment effect on intracranial and extracranial tumor–immune microenvironments (TIME) was evaluated using immunofluorescence, multiplex immunoassays, high-parameter flow cytometry, and T-cell receptor profiling. Mice with humanized immune systems were evaluated using flow cytometry to study the effect of CDKi on human T-cell development. Results: We found that combining abemaciclib with PD-1 inhibition reduced tumor burden and improved overall survival in mice. The TIME, which differed on the basis of anatomic location of tumors, was altered with CDKi and PD-1 inhibition in an organ-specific manner. Combination abemaciclib and anti–PD-1 treatment increased recruitment and expansion of CD8+ effector T-cell subsets, depleted CD4+ regulatory T (Treg) cells, and reduced levels of immunosuppressive cytokines in intracranial tumors. In immunodeficient mice engrafted with human immune systems, abemaciclib treatment supported development and maintenance of CD8+ T cells and depleted Treg cells. Conclusions: Our results highlight the distinct properties of intracranial and extracranial tumors and support clinical investigation of combination CDK4/6 and PD-1 inhibition in patients with brain metastases. See related commentary by Margolin, p. 257
FcγRIIB expressed on CD8<sup>+</sup>T cells limits responsiveness to PD-1 checkpoint inhibition in cancer
Authors: Kelsey B. Bennion, Marvi Tariq, Megan M. Wyatt, Charlotte Duneton, Kirsten M. Baecher, Chrystal M. Paulos, Ragini R. Kudchadkar, Michael C. Lowe, Mandy L. Ford
Journal: Science Translational Medicine (2023)

Checkpoint inhibition using Fc-containing monoclonal antibodies has emerged as a powerful therapeutic approach to augment antitumor immunity. We recently showed that FcγRIIB, the only inhibitory IgG-Fc receptor, is expressed on a population of highly differentiated effector CD8 + T cells in the tumors of mice and humans, raising the possibility that CD8 + T cell responses may be directly modulated by checkpoint inhibitor binding to T cell–expressed FcγRIIB. Here, we show that despite exhibiting strong proliferative and cytokine responses at baseline, human FcγRIIB pos CD8 + T cells exhibited reduced responsiveness to both PD-1 and CTLA-4 checkpoint inhibition as compared with FcγRIIB neg CD8 + T cells in vitro. Moreover, frequencies of FcγRIIB pos CD8 + T cells were reduced after treatment of patients with melanoma with nivolumab in vivo. This reduced responsiveness was FcγRIIB dependent, because conditional genetic deletion of FcγRIIB on tumor-specific CD8 + T cells improved response to checkpoint blockade in B16 and LLC mouse models of cancer. The limited responsiveness of FcγRIIB pos CD8 + T cells was also dependent on an intact Fc region of the checkpoint inhibitor, in that treatment with Fc-devoid anti–PD-1 F(ab) fragments resulted in increased proliferation of FcγRIIB pos CD8 + T cells, without altering the response of FcγRIIB neg CD8 + T cells. Last, the addition of FcγRIIB blockade improved efficacy of PD-1 checkpoint inhibition in mouse models of melanoma, lung, and colon cancer. These results illuminate an FcγRIIB-mediated, cell-autonomous mechanism of CD8 + T cell suppression, which limits the efficacy of checkpoint inhibitors during antitumor immune responses in vivo.
In Vitro 3D Spheroid Culture System Displays Sustained T Cell-dependent CLL Proliferation and Survival
Authors: Marco V. Haselager, Bianca F. van Driel, Eduard Perelaer, Dennis de Rooij, Danial Lashgari, Remco Loos, Arnon P. Kater, Perry D. Moerland, Eric Eldering
Journal: HemaSphere (2023)

Chronic lymphocytic leukemia (CLL) cells are highly dependent on microenvironmental cells and signals. The lymph node (LN) is the critical site of in vivo CLL proliferation and development of resistance to both chemotherapy and targeted agents. We present a new model that incorporates key aspects of the CLL LN, which enables investigation of CLL cells in the context of a protective niche. We describe a three-dimensional (3D) in vitro culture system using ultra-low attachment plates to create spheroids of CLL cells derived from peripheral blood. Starting from CLL:T cell ratios as observed in LN samples, CLL activation was induced by either direct stimulation and/or indirectly via T cells. Compared with two-dimensional cultures, 3D cultures promoted CLL proliferation in a T cell-dependent manner, and enabled expansion for up to 7 weeks, including the formation of follicle-like structures after several weeks of culture. This model enables high-throughput drug screening, of which we describe response to Btk inhibition, venetoclax resistance, and T cell-mediated cytotoxicity as examples. In summary, we present the first LN-mimicking in vitro 3D culture for primary CLL, which enables readouts such as real-time drug screens, kinetic growth assays, and spatial localization. This is the first in vitro CLL system that allows testing of response and resistance to venetoclax and Bruton's tyrosine kinase inhibitors in the context of the tumor microenvironment, thereby opening up new possibilities for clinically useful applications.
Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasia in close proximity to esophageal varices: a multicenter international experience
Authors: Shruti Mony, Bing Hu, Abel Joseph, Hiroyuki Aihara, Lorenzo Ferri, Amit Bhatt, Amit Mehta, Peng-Sheng Ting, Alex Chen, Andrew Kalra, Jad Farha, Manabu Onimaru, Long He, Qi Luo, Andrew Y. Wang, Haruhiro Inoue, Saowanee Ngamruengphong
Journal: Endoscopy (2023)

BACKGROUND : There are limited data on the feasibility of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) located at or adjacent to esophageal varices. We aimed to evaluate the outcomes of ESD in these patients.
Use of atrial septal occluder in the treatment of chronic fistula following post-esophagectomy anastomotic leak
Authors: Manisha Daminda Kariyawasam, Jonathan Liang Yap, Zehao Tan, Tiffany Lye, Weng Hoong Chan, Jeremy Tian Hui Tan, Chin Hong Lim
Journal: Endoscopy (2023)

Therapeutic endoscopy plays a key role in the management of gastrointestinal fistulae. Endoscopic interventions with stents [1], endoscopic clips, vacuum therapy [2], etc. have revolutionized the management of post-surgical anastomotic leaks.
PB2471: EFFECT OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION WITH MODIFIED FC PRETREATMENT REGIMEN ON SEX HORMONE LEVELS IN CHILDREN WITH SEVERE APLASTIC ANEMIA
Authors: Liangming MA, Keru Shi, Dan Wang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Allogenic hematopoietic stem cell transplantation is the most effective method to cure severe aplastic anemia. Different pretreatment schemes will have different effects on the gonadal fanction of the recipient. We adopted improved FC pretreatment scheme to treatment the patients of severe aplastic anemia, observed the gonadal fanction and survival of the patients. Aims: To observe the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a modified FC pretreatment regimen (combining low-dose Cy with ATG and Flu) on postoperative sex hormone levels in children with severe aplastic anemia (Severe Aplastic Anemia, SAA). Methods: Retrospective analysis of 37 paediatric patients with SAA who had their first allo-HSCT in our department from January 2016 to October 2022. Among these patients, 23 patients adopted the modified FC pretreatment regimen in the observation group, and 14 patients adopted the Bu-based pulp clearing pretreatment regimen in the control group. Patients’ sex hormone levels were monitored beyond 6 months after allo-HSCT to see if there were differences between the two groups of SAA patients and between them and normal children. Results: Compared with the control group, FSH of the two groups of girl patients was different, and the results were statistically significant (P<0.05).There was no statistically significant difference between the observation group and normal children. Comparing the control group of girls with the normal girls, the two groups were different in the FSH and LH two indicators, and the results were statistically significant (P=0.003, P=0.043). The SAA patients in the observation group were further divided into two groups according to the sex-matching or mismatching of the donor and the recipient. The number of male patients was small and no comparability existed. There was no significant difference in sex hormone levels between gender-mismatched girl patients and gender-matched girl patients (all six items of sex hormones were P>0.05). Summary/Conclusion: The modified FC pretreatment regimen has no significant effect on the postoperative sex hormone levels of SAA children treated with allo-HSCT.Keywords: Allogeneic hematopoietic stem cell transplant, Children, Severe aplastic anemia
PB2230: THE ORIGIN IN PRIMARY AND SECONDARY MYELOFIBROSIS: IS THE KEY THE PROGENITOR OR THE MOLECULAR SIGNATURE?
Authors: Isabel Montero Cuadrado
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Myelofibrosis (MF) is a clonal hematological malignancy which originates al the level of the pluripotent hematopoietic stem cell being the mediators of stimulation of fibroblast proliferation derived from megakaryocytes and monocytes. MF can present de novo as primary myelofibrosis (PMF) or can be secondary to an antecedent polycythemia vera (PV) or essential thrombocytosis (ET). Recognition of the driver mutations JAK2 V617F, CALR, and MPL has led to the development of ruxolitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2 that has transformed therapy for myelofibrosis. Aims: From a clinical database of 149 patients, we studied the differences between those with PMF and secondary myelofibrosis (SMF) regarding epidemiological data, molecular status, ruxolitinib response and survival. Methods: Diagnosis of primary MF (PMF) an post-Essential Thrombocytemia/post-Polycithemic MF was made according to the WHO 2016. Molecular tests for detection for JAK2, MPL and CALR mutations were performed. Ruxolitinib starting dose was decided accordingly to prescribing information.Survival analysis was performed by means of Kaplan-Meier curves and differences between KM curves were evaluated using the Log-rank test. P values less than 0.05 were considered satistically significant. Analyses were performed with SPSS software v.15. Results: Median age was 64 years (range 36–88); median haemoglobin was 110 g/l (range, 60–157) and 48,1% patients had a transfusion-dependent anemia. Median platelet an leucocyte counts were respectively 311 × 109/l (range, 52–1887) and 14,8 × 109/l (range, 52–1887). 54,5% patients have a PMF diagnosis. JAK2V617F was present in 69,8% patients, CALR mutations in 15,4% and MPLW515K/L in 5,3%; 9,5%of the patients were triple negatives. In SMF patients the median values of age, leucocytes, hemoglobin and platelets were 66 years, 12,5x10e9/L, 10,7g/dl and 259x10e9/L respectively and in PMF patients 66 years, 8,9x10e9/L, 10,7x10e9/L and 243x10e9/L, without statistical differences between both groups. Fifty five patients were treated with ruxolitinib, 30 in PMF group and 25 in SMF group. 86% of patients had a response to this treatment.. The median survival at five years was 71%, 81% in SMF and 69% in PMF. In patients with CALR mutations, the survival was poor in PMF (34%) than in posthrombocitemic MF(80%) without differences in JAK2V617F mutated group. Summary/Conclusion: Ruxolitinib is an effective treatment in PMF and SMF with a favorable impact in survival. 2.-In CARL mutated patients, the hematopoietic progenitor seems to be more sensitive to JAK2 pathway blocking when the disease has evolutioned from a previous ET although large studies are required to confirm these results. Keywords: Myelofibrosis, Myeloid metaplasia, Idiopathic myelofibrosis
PB2161: BORTEZOMIB, POMALIDOMIDE, AND DEXAMETHASONE IS AN EFFECTIVE REGIMEN FOR PATIENTS WITH RELAPSE AND REFRACTORY AL AMYLOIDOSIS AND MONOCLONAL IMMUNOGLOBULIN DEPOSITION DISEASE
Authors: Yang Liu, Qike Zhang, Lei Wen, Shasha Wang, Xuelin Dou, Xiaojun Huang, Jin Lu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: There needs for treatment of recurrent and refractory amyloidosis or monoclonal immunoglobulin deposition disease (MIDD) are still unmet. Aims: The efficacy and safety of treatment with bortezomib, pomalidomide, and dexamethasone (BPd) as second-line treatment for AL amyloidosis or MIDD were reported. Methods: Recurrent or refractory primary AL/AHL amyloidosis amyloidosis or MIDD patients receiving BPd from Jan 2021 to March 2022 were retrospectively collected. Results: Twenty-one patients were treated for a median of 3 cycles (range, 1-8). The median difference between involved and uninvolved free light chains (dFLC) before BPd initiation was 111.2 (IQR, 62.8-885.0), with a decrease in median value of 19 (IQR: 7.0-122.3). 14/21 patients had a hematologic response, with 3/21 complete response, 9/21 very good partial response, with 7 of these 21 patients achieving an organ response. Toxicity was minimal and no patient had a treatment-related death. During a median follow-up period of five months one patient died of chocking and suffocation.Summary/Conclusion: BPd is well tolerated with few side effects and warrants continued investigation as a treatment for AL amyloidosis. Keywords: Amyloidosis
PB1963: PSYCHIATRIC DISORDERS AS A FIRST MANIFESTATION OF SPORADIC CREUTZFELDT-JACOB DISEASE IN A PATIENT WITH CHRONIC MYELOID LEUKEMIA ON IMATINIB: UNUSUAL AND LIFE THREATENING ASSOCIATION
Authors: Rachid Smaili, Myriem Bourkia
Journal: HemaSphere (2023)

Topic: 7. Chronic myeloid leukemia - Biology & Translational Research Background: Creutzfeldt Jakob disease (CJD) is on of the fatal and rare neurodegenerative disease, It is classified into 3 subgroups: sporadic, genetic and acquired. Sporadic CJD is the most common form, which may be manifested with misleading neuropsychiatric symptoms and resulting in death within 6 to 12 months. Several treatments have failed in sporadic CJD, while ‘imatinib mesylate’, the first drug to target the Bcr-Abl pathway in chronic myeloid leukemia (CML), has been demonstrated to be effective against prion protein aggregation in experimental model Aims: To describe the first case of sporadic Creutzfeldt Jakob disease (CJD) in a patient with Bcr-ABL-positive chronic myeloid leukemia who presented with a psychiatric symptoms and survived more than two years on “imatinib mesylate” treatmen Methods: A 60-year-old female without any medical history of neuropsychiatric disorders, diagnosed for Bcr-Abl positive chronic myeloid leukemia two years ago with hematological remission under imatinib treatment. Who presented with major depression with unexplained changes in behavior by her member of family, eating disorders for which was put on antipsychotic medication for 12 months, with a progressive onset of dementia and extrapyramidal syndrome of the upper limb. A brain CT scan, metabolic assessment and vitamin dosages were normal. The patient was treated as a parkinsonism with L-dopa in addition to psychiatric drugs over six months with initial improvement and then progressive worsening of the extrapyramidal syndrome, associated with myoclonus, visual disturbance. MRI Brain was performed and demonstrated bilateral symmetrical hypersignals of the striatum (fig. 1). The electroencephalogram showed a theta rhythm and triphasic periodic abnormalities. A CSF test for 14.3.3 was positive. A diagnosis of probable sporadic CJD was made. Imatinib mesylate was majored to 800mg/day in addition to symptomatic treatment. Patient died died eight months later from an akinetic coma. Results: Over two years of survival-term in a patient with sporadic CJD and Bcr-Abl positive chronic myeloid leukemia on imatinib mesylate treatment. Summary/Conclusion: This clinical presentation is nonspecific and the association is exceptional of MCL ans CJD, making the diagnosis very challenging in patient with heamatologic neoplasm. However, the combination of this clinical presentation with MRI-imaging, lumbar puncture and encephalogram are helpful. The prolonged survival over two years in our patient suggested that imatinib is a promising treatment in sporadic CJD.Fig.1: Magnetic resonance imaging: fluid attenuated inversion recovery (FLAIR) and T2 weighted pulse sequences revealed bilateral and symmetrical hyper-intensities in the caudate nucleus and putamen. Keywords: Janus Kinase inhibitor, Imatinib, Chronic myeloid leukemia
PB2164: EFFICACY AND SAFETY EVALUATION OF IXAZOMIB, POMALIDOMIDE, AND DEXAMETHASONE IN THE TREATMENT OF RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: Wen LI, Zhipeng Zhang, Zhigang Zhou, Hong Liu, Hongming Huang, Kai Lu, Haijuan Ren, Zenghua Lin
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Relapsed/refractory multiple myeloma(RRMM) is a malignant disease with abnormal proliferation of clonal plasma cells. With the use of autologous stem cell transplantation and new drugs in the first-line therapy, the survival rate of MM patients has improved significantly. However, MM is still an incurable disease and patients will eventually face recurrence. In view of the impact of the Corona Virus Disease 2019(COVID-19), many patients can not get regular treatment. Delaying or even interrupting treatment has become the biggest difficulty in the disease progression of MM. Therefore, it is urgent to seek safe and convenient all-oral chemotherapy regimens. Aims: To evaluate the efficacy and safety of Ixazomib, Pomalomide and dexamethasone(IPD) in the treatment of relapsed/refractory multiple myeloma(RRMM) retrospectively. Methods: We enrolled 11 patients with RRMM who received at least 4 courses of IPD in the Department of Hematology, Affiliated Hospital and Medical School of Nantong University from January 2021 to July 2022, and analyzed the efficacy and safety after medication. Results: The number of presequencing lines in the patients included in the study ranged from 1 to 4, and the main reasons for switching to IPD were relapse, progression, and COVID-19. In ≥4 courses of treatment, the all-oral IPD was discontinued after progression in 3 of 9 patients with evaluable efficacy. Among the 2 patients that in stable disease(SD), one case continued to take medication while another changed to Daratumumab-Ixazomib-dexamethasone(DID) due to their own will. The remaining 5 patients who responded to IPD continued to take medication. Summary/Conclusion: Under the trend of the COVID-19 pandemic, the all-oral IPD treatment has better efficacy and safety, and is more stable and convenient. However, due to the limited cases, the strength of relevant clinical suggestions needs to be further confirmed by expanding the sample size and multi-center studies. Keywords: Relapse, Treatment, Refractory, Multiple myeloma